生物谷報(bào)道:來(lái)自匹茲堡大學(xué)癌癥研究院(University of Pittsburgh Cancer Institute)分子病毒研究組的研究人員提出了一種尋找人類病毒的新方法:他們發(fā)現(xiàn)引起卡波濟(jì)氏肉瘤(Kaposi’s Sarcoma,,生物谷注)的原因是之前未知的一種病毒,這種病毒與另一少見(jiàn),,但是致命的皮膚癌——Merkel細(xì)胞癌(merkel cell carcinoma,,www.ebiotrade.com)密切相關(guān),。這一研究成果公布在上周五(1月18日)出版的Science在線版上。
領(lǐng)導(dǎo)這一研究,,文章的通訊作者是癌癥研究院KSHV實(shí)驗(yàn)室的Patrick S. Moore與Yuan Chang,,這兩位分子病毒學(xué)領(lǐng)域的專家教授是一對(duì)夫妻,前者畢業(yè)于斯坦福大學(xué),,實(shí)驗(yàn)室主要興趣在于研究KSHV與宿主信號(hào)途徑之間的基礎(chǔ)關(guān)系,。
這一新獲得的研究成果花費(fèi)了他們十年的時(shí)間,,利用測(cè)序技術(shù)識(shí)別這種MCV病毒(Merkel cell polyomavirus),這也許能提供一種新的癌癥治療及預(yù)防措施,。
Moore博士表示,,“這是第一個(gè)發(fā)現(xiàn)的與某種特殊類型的人類腫瘤密切相關(guān)的多瘤病毒(polyomavirus,www.ebiotrade.com)”——多瘤病毒PY能誘發(fā)多個(gè)部位或器官發(fā)生肉瘤或癌癥,,因此稱為多瘤病毒,,“雖然多瘤病毒在癌癥發(fā)育方面已經(jīng)研究了多年,,但是許多重要證據(jù)都表明這些病毒并不會(huì)引發(fā)人類癌癥,。”
Merkel細(xì)胞癌(MCC)是原發(fā)于皮膚的一種高度惡性腫瘤,1972年Toker首先描述并用”梁狀癌”命名,,因其腫瘤細(xì)胞質(zhì)內(nèi)有神經(jīng)內(nèi)分泌顆粒出現(xiàn),,也被稱作原發(fā)于皮膚的神經(jīng)內(nèi)分泌癌,。主要發(fā)生于老年人的頭頸部及四肢,具有獨(dú)特的超微結(jié)構(gòu)改變和免疫組化染色特征,。在過(guò)去的20年間,,MCC增長(zhǎng)了三倍,每年出現(xiàn)1500個(gè)病例,,這種癌癥主要發(fā)生在免疫系統(tǒng)受到AIDS,,或者移植相關(guān)免疫抑制藥物破壞的個(gè)體身上,一半患有MCC的病人只能存活至多9個(gè)月,,三分之二的病人在5年內(nèi)會(huì)死亡,。
“如果我們的這些研究成果得到進(jìn)一步證實(shí),我們就能了解這種新病毒是如何導(dǎo)致這一高致死率的癌癥的發(fā)生,,而且重要的是,,利用這一模式,我們能了解癌癥發(fā)生,,及其癌癥發(fā)生過(guò)程中的細(xì)胞途徑的變化”,,Moore博士說(shuō)。
生物谷推薦原始出處:
Published Online January 17, 2008
Science DOI: 10.1126/science.1152586
Submitted on November 5, 2007
Accepted on January 8, 2008
Clonal Integration of a Polyomavirus in Human Merkel Cell Carcinoma
Huichen Feng 1, Masahiro Shuda 1, Yuan Chang 1*, Patrick S. Moore 1*
1 Molecular Virology Program, University of Pittsburgh Cancer Institute, University of Pittsburgh, 5117 Centre Ave, Suite 1.8, Pittsburgh, PA 15213, USA.
* To whom correspondence should be addressed.
Yuan Chang , E-mail: yc70@pitt.edu
Patrick S. Moore , E-mail: psm9@pitt.edu
These authors contributed equally to this work.
Merkel cell carcinoma (MCC) is a rare but aggressive human skin cancer that typically affects elderly and immunosuppressed individuals, a feature suggestive of an infectious origin. We studied MCC samples by digital transcriptome subtraction (DTS) and detected a fusion transcript between a previously undescribed virus T antigen and a human receptor tyrosine phosphatase. Further investigation led to discovery and sequence analysis of the 5387-base-pair genome of a new polyomavirus that we call Merkel cell polyomavirus (MCV or MCPyV). MCV sequences were detected in 8 of 10 (80%) MCC tumors but in only 5 of 59 (8%) control tissues from various body sites and 4 of 25 (16%) control skin tissues. In six of 8 MCV-positive MCCs, viral DNA was integrated within the tumor genome in a pattern suggesting that MCV infection/integration preceded clonal expansion of the tumor cells. Thus, MCV may be a contributing factor in the pathogenesis of MCC.